NM_080704.4:c.254A>G

Variant names:

• chr17-3592097-T-C
• rs55916885
• NM_080704.4:c.254A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080704.4(TRPV1):​c.254A>G​(p.Gln85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,646 control chromosomes in the GnomAD database, including 1,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (58 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1031 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 19 publications found

Genes affected

TRPV1 (HGNC:12716): (transient receptor potential cation channel subfamily V member 1) Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5' UTR sequence, have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000262304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002980262).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.254A>G	p.Gln85Arg	missense_variant	Exon 3 of 17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.254A>G	p.Gln85Arg	missense_variant	Exon 2 of 16		NP_061197.4
TRPV1	NM_080705.4	c.254A>G	p.Gln85Arg	missense_variant	Exon 2 of 16		NP_542436.2
TRPV1	NM_080706.3	c.254A>G	p.Gln85Arg	missense_variant	Exon 1 of 15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.254A>G	p.Gln85Arg	missense_variant	Exon 3 of 17	1	NM_080704.4	ENSP00000459962.1
ENSG00000262304	ENST00000572919.1	n.*1538A>G		non_coding_transcript_exon_variant	Exon 8 of 14	5		ENSP00000461416.1
ENSG00000262304	ENST00000572919.1	n.*1538A>G		3_prime_UTR_variant	Exon 8 of 14	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3868 AN: 152142 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00692

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0280 AC: 6941 AN: 247646 AF XY: 0.0288

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0455

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0476

Gnomad NFE exome AF: 0.0351

Gnomad OTH exome AF: 0.0301

GnomAD4 exome AF: 0.0348 AC: 50818 AN: 1461388 Hom.: 1031 Cov.: 32 AF XY: 0.0345 AC XY: 25056 AN XY: 726968

African (AFR) AF: 0.00544 AC: 182 AN: 33480

American (AMR) AF: 0.0155 AC: 693 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 1216 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0253 AC: 2180 AN: 86248

European-Finnish (FIN) AF: 0.0474 AC: 2521 AN: 53230

Middle Eastern (MID) AF: 0.0643 AC: 370 AN: 5750

European-Non Finnish (NFE) AF: 0.0375 AC: 41656 AN: 1111786

Other (OTH) AF: 0.0331 AC: 1996 AN: 60362

GnomAD4 genome AF: 0.0254 AC: 3867 AN: 152258 Hom.: 58 Cov.: 32 AF XY: 0.0255 AC XY: 1901 AN XY: 74448

African (AFR) AF: 0.00690 AC: 287 AN: 41568

American (AMR) AF: 0.0156 AC: 239 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4824

European-Finnish (FIN) AF: 0.0462 AC: 491 AN: 10624

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0363 AC: 2466 AN: 67998

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0320 Hom.: 278

Bravo AF: 0.0220

TwinsUK AF: 0.0369 AC: 137

ALSPAC AF: 0.0345 AC: 133

ESP6500AA AF: 0.00766 AC: 31

ESP6500EA AF: 0.0327 AC: 273

ExAC AF: 0.0270 AC: 3265

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.0330

EpiControl AF: 0.0329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.1
DANN	Benign	0.88
DEOGEN2	Benign	0.29	T;T;T;T;.;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.56	.;.;.;T;T;T;T
MetaRNN	Benign	0.0030	T;T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.2	L;L;L;L;.;.;.
PhyloP100		-0.98
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.96	N;.;.;N;N;.;N
REVEL	Benign	0.022
Sift	Benign	0.21	T;.;.;T;T;.;T
Sift4G	Benign	0.59	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.;B
Vest4		0.054
MPC		0.069
ClinPred		0.0012	T
GERP RS		-2.6
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.34
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55916885; hg19: chr17-3495391; COSMIC: COSV107184713;